Hepcidin is the master regulator of iron homeostasis. In anaemia of chronic disease (ACD), hepcidin is elevated. The mechanism by which elevated hepcidin causes iron restriction is:
- A Hepcidin inhibits DMT-1 (divalent metal transporter-1), blocking intestinal iron absorption
- B Hepcidin binds transferrin, preventing it from delivering iron to bone marrow erythroblasts
- C Hepcidin binds and causes degradation of ferroportin, the sole iron exporter on enterocytes and macrophages, trapping iron intracellularly ✓
- D Hepcidin activates ferritin synthesis, sequestering iron in hepatocytes
Correct answer: C. Hepcidin binds and causes degradation of ferroportin, the sole iron exporter on enterocytes and macrophages, trapping iron intracellularly
Explanation
Hepcidin, a 25-amino acid peptide produced by the liver, binds to ferroportin (SLC40A1), the only known mammalian iron export protein found on enterocytes, hepatocytes, and reticuloendothelial macrophages. Hepcidin binding induces ferroportin internalisation and lysosomal degradation, trapping iron within cells. In ACD, IL-6 (from inflammation) upregulates hepcidin via JAK/STAT3–HAMP gene pathway, restricting iron for erythropoiesis. In hereditary haemochromatosis, hepcidin deficiency permits excess ferroportin activity and iron overload.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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